Where were you before coming to OHSU?

I came from Stanford. Much of the work I did there was in human embryology, and my focus was on aneuploidy—the loss or gain of whole chromosomes—and how it impacts in-vitro fertilization (IVF) success. IVF has been around over 35 years and is still only 30-35% successful. One thing that’s thought to be problematic, not just with IVF, but with human fecundity in general, is why we exhibit high rates of embryonic loss following IVF as well as naturally, often even before a woman would know she’s pregnant. At least 50-80% of all embryos at the cleavage stage—that is, early cell division—will have at least one chromosome affected and will probably arrest at the 8-cell stage, making them unviable. About a million embryos are produced for IVF every year in the U.S. alone, and many of them will not result in a successful pregnancy. I want to identify those that are destined to fail before they’re implanted.

What brought you to OHSU?

There are some things we can’t do with human embryos, whether it’s procuring samples, being able to establish cell lines, or other exploratory research, so the primate center was key in my decision. I had never worked with monkeys before so coming here was a real challenge, as I had to learn about rhesus physiology. But the more I delved into the literature and the work we’re doing in the lab, the more I realized I landed in the right place. Aneuploidy rates in rhesus macaque are very similar to those in humans and female rhesus macaques have comparable reproductive physiology and cycles to human females. Also, there are strict timing intervals of mitotic divisions that indicate whether an embryo will be chromosomally normal or abnormal. These intervals may be slightly faster in the macaque but the dynamics are identical. By contrast, though much research in this area has been conducted using a mouse model, mice exhibit only around 1-10% aneuploidy. Macaques are the perfect model for my work and unlike mice, are released back to the colony following IVF.

What specific avenues of research are you exploring?

Examining cellular fragmentation more closely. Between the 1 and 2 cell stage is when you see these fragments form. They appear as small cytoplasmic balls that were thought to be empty, but we now know they can contain chromosomes. It appears fragmentation is in response to aneuploidy. What we don’t know is it trying to correct aneuploidy or trying to initiate its demise?

Rhesus embryo with fragmentationPhoto by Cathy Ramsey

DNA sequencing can now be done on a single cell level. So what we’re doing is taking 8 cell embryos and disassembling them into single cells and single fragments. In collaboration with Lucia Carbone, who investigates chromosomal rearrangements, we are DNA sequencing the whole embryo to try to reconstruct what has happened. Is there a mitotic or a meiotic error? Are there whole chromosomes or pieces missing? What is the structure of the chromosomes that remain? These are things we don’t know and are trying to find out. Being able to combine a single cell approach to answer some of the basic questions with time-lapse imaging, DNA sequencing, and gene expression allows us to correlate the data to get an idea of the full dynamic. We then hope to use these results to determine whether there are natural mechanisms such as multi-polar cell divisions or the resorption of fragments that we could exploit or other potential therapeutic interventions for improving IVF success.

We’re also looking into the male’s contribution to aneuploidy, which I think we have probably underestimated in the past.

What is your overall goal for the research you’re doing now?

To improve IVF. I’ve met infertile couples and worked with them and all they want is a baby. The cost is enormous – $12K for each cycle – and of course the emotional toll of going through multiple cycles without success… There’s no price tag for that. A lot of people I speak to suggest these couples should just adopt. But what they don’t know is that adoption, both here in the US and abroad has become more and more difficult. My real hope is that we can improve IVF so that we get to a point where we transfer one embryo and get one baby. Right now, we’re transferring more than one embryo to maximize the chance of success but this also increases the chance of multiples which carries with it a great deal of risk for both the mother and babies.

What other avenues of research interest you?

I would love to extend what we’ve learned about IVF and use it to work in conservation biology. A number of species are nearly extinct and IVF could be used to help maintain their populations. I’d also like to investigate the aneuploidy variability between species. I’m interested in evolutionary questions about why different species evolved to be more or less successful at reproduction.

Tell us something about your career that’s not on your CV.

In college, I took a course in developmental biology and we did sea urchin fertilization and I thought it was the most amazing thing ever! This is really what set me on my course.

What do you like to do for fun?

Spend time with my two daughters. I like to run a lot and am I going to try to do the Portland marathon in the fall – I haven’t done one in a while. We also spend a lot of time in our garden. I’m just really enjoying Portland. The way of life is excellent here and I wish we’d made the move sooner.